Canine Solution: How Canine Genetics Influence Human Medicine

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A Labrador Retriever is much more likely to suffer an anterior cruciate ligament rupture than a Greyhound. While both races are Canis lupus familiarisdifferent dog breeds have different predispositions to disease, which can be key to understanding and treating similar diseases in humans.

A byproduct of domestication

Around 10,000 years ago, the relationship between wolves and humans began to change. From enemy to friend, domestication gave way to village dogs, which lived within human communities. As the relationship between humans and dogs evolved, increasing selective pressures were applied, and these resulted in phenotypic changes, particularly in appearance and behavior.

Over the past few centuries, intense selective breeding pressure over a short period of time has created many different phenotypes and the over 400 dog breeds of varying morphology that we know today. However, unwanted genetic variants have also been inadvertently enriched in specific breeds, making different breeds more protected or more vulnerable to specific diseases.

These different levels of disease susceptibility are the focus of research by Peter Muir, a veterinary clinician-scientist, surgeon, and researcher in the Department of Surgical Sciences at the University of Wisconsin School of Veterinary Medicine and an affiliate member of the Center for Genomic Science Innovation University. of Wisconsin-Madison.

His lab uses a variety of genomic approaches, such as genome-wide association studies, transcriptomics, and whole genome sequencing analysis to identify genetic causes of disease in companion animals. By analyzing diseases such as anterior cruciate ligament rupture, laryngeal paralysis and fibrotic myopathy, he aims to discover new genetic contributions to the disease and to develop genetic tests for these conditions in dogs that will improve veterinary care for these patients.

phenotypic: relating to the set of observable characteristics of an animal or other organism resulting from the interaction of its genome with the environment

morphology: the study and categorization of the shape and form of an organism

transcriptomics: a method that allows the study of the complete set of RNA genetic sequences

Mendelian: a term to describe common patterns of inheritance

pleiotropy: a phenomenon in which a single gene influences several distinct traits through the sharing of genetic variants

genetic variant: permanent change in the DNA sequence that makes up a gene

Impact on dogs

“In the world of veterinary medicine, there’s a lot of interest in developing tests to genotype dogs to see if they carry certain mutations,” says Muir. This information may be useful not only to breeders so that they can avoid carriers or people at high genetic risk when breeding, but also to the dog-owning public, as dogs identified as high risk for certain genetic diseases may benefit from personalized care or preventive treatment.

However, studying these diseases in dogs may also be essential for treating humans. for example, in the case of Mendelian diseases. These diseases occur when specific gene mutations are passed on to subsequent generations. Well-known examples include cystic fibrosis and sickle cell disease.

“Mendelian disease, like Duchenne muscular dystrophy, affects both humans and dogs. The mutation causing this disease is present in the same gene in both species”, illustrates Muir. “The mutation isn’t the same, but humans and dogs develop a similar disease, so the idea that the disease in dogs functions as a model for each other isn’t hard to grasp.”

Translation search

Laryngeal paralysis and fibrotic myopathy are also similar to related diseases in humans. The discovery of a new genetic effect in dogs could help human genomics researchers advance work in this area to make more discoveries in the human equivalent disease.

“If there is a genetic disease that has a phenotype and a pharmaceutical company is interested in a disease-modifying treatment, it is much easier and cheaper to confirm its effectiveness in a canine model than to conduct trials in the man,” says Muir. “And these studies also offer benefits for dogs.”

There is a wide range of diseases in humans that have a dog counterpart: Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy affecting 1 in 2,500 humans, is similar to laryngeal paralysis polyneuropathy in dogs, the most common. canine hereditary peripheral neuropathy, which causes partial airway obstruction in dogs. CMT currently has no disease-modifying treatment, so finding a treatment in dogs could prove crucial for humans with peripheral neuropathy.

Unlike Mendelian diseases, it is more difficult to use dogs as animal models for complex diseases. Pleiotropy and variant sharing between related complex diseases may cause some genetic variants to be a risk factor for more than one related complex disease in humans, and currently there is no global approach for the analysis of the sharing of variants between the two species. Yet, as new methods are developed, the argument that complex diseases in animals are good models for equivalent human diseases will be strengthened.

To be involved

Unlike research with model organisms where animals are kept in the laboratory, companion animal research relies on the community of dog owners to help them conduct their studies.

“People on this campus know where the veterinary school building is, but they don’t always know that there is a small animal hospital with over 25,000 patient admissions a year, and that is a valuable resource for scientific research,” says Muir.

Dog, cat and horse owners interested in getting involved should check out their Facebook page, where the lab posts articles detailing the pets they could recruit for their research.

Leonardo Barolo Gargiulo

Reproduced with permission from the Center for Genomic Science Innovation.
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